PROJECT SUMMARY/ABSTRACT With the remarkable capacity to form complete individuals from tiny body fragments, planarian flatworms represent a valuable model organism for research on cellular and molecular mechanisms of regeneration. One important objective in this field is to determine how changes in gene expression are triggered in response to injury, in order to initiate the regenerative response. The overall goal of this project is to addresses the hypothesis that the nonsense-mediated mRNA decay pathway (NMD), a cellular surveillance mechanism with emerging roles in stem cells and their division progeny, orchestrates posttranscriptional control of gene expression during regeneration. Specific aims include 1) analyzing the effects of RNAi knockdown of conserved NMD factors on cellular events that occur following amputation, including stem cell proliferation and migration to the wound site; 2) identifying planarian NMD target mRNAs through an RNA-Seq approach, and determining their specific functions using RNAi and in situ hybridization; and 3) determining how specific transcripts are designated for NMD. Completion of the proposed objectives will improve our understanding of how gene expression is regulated during regeneration, and has the potential to reveal new avenues for clinical intervention in the treatment of human injury or degenerative disease. Additionally, the project will afford undergraduate students at Keene State College an opportunity to engage in discovery- based research relevant to the rapidly growing field of regenerative medicine.